Genetic and environmental factors interact in the development of autoimmune disease in mouse and man. In the mouse, two autosomal recessive mutations, lpr and gld, contribute to syndromes characterized by production of lymphoproliferation and autoantibodies. To evaluate mechanisms by which these mutations result in autoimmunity, we have initiated attempts to molecularly clone the gld locus and have studied lymphokine production by the abnormal Thy-1+, Ly-2-, Ly-4- cells that accumulate in tissues of the mice. To facilitate cloning gld, a molecular map of distal mouse chromosome 1 is being generated and gld has been shown to map in close proximity to the At-3 locus. Studies of lymphokine-specific mRNA species in the abnormal T cells of lpr and gld mice have shown that they do not express signigicant levels of message for IL-6, IL-5, IL-4, TNF, or GM-CSF. Neuroleukin was expressed in both cell types at levels equivalent to normal T cells. Further studies are required to determine how these unusual cells participate in the development of autoimmunity.